1. Technical Field of the Invention
The present invention relates to a novel method for the preparation of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2naphthoic acid of formula (I):
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2. Description of Background and/or Related and/or Prior Art
The compound of formula (I) is described in particular in EP-0,199,636. EP-0,199,636 describes the preparation of this compound according to the following Scheme 1:

In this method, 2-(1-adamantyl)-4-bromoanisole is converted, in a first step (a), to its organomagnesium compound, and then to its organozinc compound by the action of zinc chloride (ZnCl2), and is then coupled with methyl 6-bromonaphthoate. This reaction is catalyzed by a transition metal (palladium or nickel) or one of its complexes with various phosphines. The synthesis of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2naphthoic acid of formula (I), as described in EP-0,199,636 (Scheme 1), is therefore carried out in three steps with a yield of 63%, from 2-adamantyl-4-bromoanisole.
One of the disadvantages of this reaction is the formation of impurities. One of these impurities results from the reaction of the organozinc compound generated “in situ” with 2-adamantyl-4-bromoanisole to give 3,3′-di(1-adamantyl)-4,4′-dimethoxy-1,1′-biphenyl having the following structure:

Another impurity also forms via the transfer of the zinc compound of 2-(1-adamantyl)-4-bromoanisole to methyl 6-bromonaphthoate and the reaction of this novel zinc compound with methyl 6-bromonaphthoate to give the dimerization product having the structure:

This product leads, after saponification (step (b)) and acidification (step (c)), to the following impurity:

A third impurity forms during the hydrolysis of the reaction medium. Indeed, during this hydrolysis, the unreacted organozinc compound of 2-(1-adamantyl)-4-bromoanisole generates the impurity having the following structure:

At an industrial stage, these impurities are difficult to remove from the finished product and most often require reprocessing by recrystallization.
Furthermore, certain catalysts such as [1,2-bis(diphenylphosphino)ethane]nickel chloride (NiCl2(dppe)) must be prepared separately, adding a step to this method.
During the coupling reaction in step (a), the acid functional group is protected in methyl ester form. This acid functional group should be regenerated. Thus, in a second step (b), methyl 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoate is saponified by treating with a base such as sodium hydroxide (NaOH) or potassium hydroxide (KOH) under reflux in an alcohol such as methanol.
By acidifying the reaction medium with hydrochloric acid, 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid is obtained in a third step (c). It should also be noted that in this method, the methyl ester of 6-bromonaphthoic acid should be prepared in one step from the corresponding acid. It can therefore be seen that the prior art method is complex and is not entirely satisfactory.